Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding

Abstract

Weight regain after caloric restriction results in accelerated fat storage in adipose tissue. This catch-up fat phenomenon is postulated to result partly from suppressed skeletal muscle thermogenesis, but the underlying mechanisms are elusive. We investigated whether the reduced rate of skeletal muscle contraction-relaxation cycle that occurs after caloric restriction persists during weight recovery and could contribute to catch-up fat. Using a rat model of semistarvation-refeeding, in which fat recovery is driven by suppressed thermogenesis, we show that contraction and relaxation of leg muscles are slower after both semistarvation and refeeding. These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers. These semistarvation-induced changes persisted during recovery and correlated with impaired expression of transcription factors involved in slow-twitch muscle development. We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility. These energy-sparing effects persist during weight recovery and contribute to catch-up fat.

Metabolic profile and spontaneous physical activity modulation under short-term food restriction in young rats.

“…That glucose uptake by the oxidative muscles also leads to an increase in glycogen stores for heart and soleus, as found in our experiment. Therefore, observing the big picture of the metabolic status, FR forced the organism balancing and reallocating substrates to survive, showing a high efficiency on energy usage, corroborating with some authors statements 4,19 . Allthose modulations of metabolic and locomotor activity discussed above have been associated with neural communication, being the neuropeptide Y (NPY) and agouti-related peptide (AgRP) signals the most involved 27,28 .…”

“…In this regard, an interesting idea of a mechanism to save energy in times of FR was proposed 8 , being recently improved by involving neuronal, endocrine and metabolic elements 4 . Whereas it is obvious that efficiency in fuel utilization of mammals is higher in long-term food restricted animals 19 , it is not clear whether differences regarding SPA also exist in short periods of FR. Furthermore, it is not known to date how FR could affect metabolic responses in young rats.…”

“…In periods of food restriction it was described a change from glycolytic to oxidative muscles 19 and it is known that the glucose uptake by the oxidative muscles increases during food restriction 25 , so, it is expected a decrease in serum glucose followed by decrease in the liver glycogen, as classically described to glycidic liver metabolism 26 . That glucose uptake by the oxidative muscles also leads to an increase in glycogen stores for heart and soleus, as found in our experiment.…”

“…In situations of negative energy balance NPY and AgRP activity increase 6 , however, during food restriction there is no possibility of feeding and it is possible that those signals persist. If correct, the consequences of chronically higher activity of NPY and AgRP in this case, with no food available, can be the inhibition of thermogenesis 24 and SPA 18 when trying to promote positive (or less negative) energy balance and maybe influencing the efficiency of energy usage 4,19 . In summary, our experiment showed that even short-term food restriction of 50% imposes significant modulations on the metabolic profile towards the use of energy stores preferably in oxidative tissues of young rats.…”

Plasticity of adipose tissue in response to fasting and refeeding in male mice

“…In addition, weight regain after fasting and subsequent ad libitum refeeding result in accelerated fat storage in adipose tissue. The “catch-up growth” might even increase the risk of developing obesity [16, 17]. Whether fasting is a causative factor in subsequent weight gain and contributes to the current obesity epidemic has been a subject of considerable debate [8].…”